Rare Metabolic Diseases Unit, MBBM Foundation, San Gerardo Hospital, Reference Centre for Hereditary Metabolic Disorders (MetabERN), Monza, Italy.
TIGET Institute, IRCCS San Raffaele Hospital, Milan, Italy.
Drug Des Devel Ther. 2020 Jun 3;14:2149-2158. doi: 10.2147/DDDT.S249433. eCollection 2020.
To determine the impact of initiating enzyme replacement therapy (ERT) with agalsidase alfa early in the course of Fabry disease, we evaluated renal and cardiac outcomes for ≤10 years after ERT initiation in males from the Fabry Outcome Survey (FOS).
Male patients from FOS were stratified into three cohorts by age at ERT initiation: ≤18 years (cohort 1), >18 and ≤30 years (cohort 2), and >30 years (cohort 3). Analysis included age at symptom onset, diagnosis, and ERT initiation; ERT duration; FOS-Mainz Severity Score Index (FOS-MSSI); estimated glomerular filtration rate (eGFR); proteinuria level; and left ventricular mass indexed to height (LVMI). Mixed-effect models estimated renal and cardiac outcomes during follow-up between and within cohorts.
The analysis included 560 male patients: 151 (27.0%) in cohort 1, 155 (27.7%) in cohort 2, and 254 (45.4%) in cohort 3. Mean±SD duration of ERT for cohorts 1, 2, and 3 was 6.3±4.3, 8.6±4.9, and 7.9±4.9 years, respectively. Mean±SD baseline FOS-MSSI scores increased with age from 9.8±7.2 in cohort 1 to 24.7±11.4 in cohort 3. Cohort 3 showed the lowest baseline mean±SD value for eGFR (87.1±29.0 mL/min/1.73m) and highest baseline mean±SD values for proteinuria (801.9±952.6 mg/day) and LVMI (56.7±16.0 g/m) among the three cohorts. Evaluation of mean annual rates of change in eGFR, proteinuria, and LVMI revealed no significant differences in any parameter for cohort 1. For cohort 2, proteinuria and LVMI remained stable, whereas eGFR significantly deteriorated annually (-1.12 mL/min/1.73m; <0.001). Cohort 3 demonstrated significant annual deteriorations in eGFR (-2.60 mL/min/1.73m; <0.001), proteinuria (+34.10 mg/day; <0.001), and LVMI (+0.59 g/m; =0.001).
Renal and/or cardiac disease progression appears attenuated in patients starting ERT in childhood or early adulthood versus patients starting ERT in later adulthood. These findings support early ERT initiation in Fabry disease. ClinicalTrials.gov identifier: NCT03289065.
通过评估 Fabry 疾病男性患者接受阿加糖酶α治疗（ERT）后≤10 年的肾脏和心脏结局，来确定在 Fabry 结局调查（FOS）中早期开始 Fabry 疾病 ERT 对疾病的影响。
根据接受 ERT 的年龄，将 FOS 中的男性患者分为三个队列：≤18 岁（队列 1）、>18 岁且≤30 岁（队列 2）和>30 岁（队列 3）。分析包括症状发作、诊断和 ERT 开始的年龄；ERT 持续时间；FOS-Mainz 严重程度评分指数（FOS-MSSI）；估算肾小球滤过率（eGFR）；蛋白尿水平；左心室质量指数（LVMI）。混合效应模型估计了队列间和队列内随访期间的肾脏和心脏结局。
该分析包括 560 名男性患者：队列 1 中 151 名（27.0%），队列 2 中 155 名（27.7%），队列 3 中 254 名（45.4%）。队列 1、2 和 3 的 ERT 平均持续时间分别为 6.3±4.3、8.6±4.9 和 7.9±4.9 年。队列 1 的 FOS-MSSI 评分的基线平均值±标准差随年龄增加，从 9.8±7.2 增加到 24.7±11.4。与其他两个队列相比，队列 3 的基线平均 eGFR 值最低（87.1±29.0 mL/min/1.73m），蛋白尿（801.9±952.6 mg/天）和 LVMI（56.7±16.0 g/m）的基线平均值最高。评估 eGFR、蛋白尿和 LVMI 的平均年变化率，发现队列 1 中没有任何参数的差异具有统计学意义。队列 2 中，蛋白尿和 LVMI 保持稳定，而 eGFR 则每年显著恶化（-1.12 mL/min/1.73m；<0.001）。队列 3 中，eGFR（-2.60 mL/min/1.73m；<0.001）、蛋白尿（+34.10 mg/天；<0.001）和 LVMI（+0.59 g/m；=0.001）的恶化具有统计学意义。
与成年后期开始 ERT 的患者相比，儿童或成年早期开始 ERT 的患者肾脏和/或心脏疾病进展似乎有所减轻。这些发现支持 Fabry 疾病的早期 ERT 治疗。临床试验标识符：NCT03289065。
